Dr. Alfred Changs laboratory has described a new method of generating sensitized T cells for adoptive immunotherapy utilizing tumor-primed lymph node cells activated sequentially by an anti-CD3 mAb and IL-2. Exhaustive animal therapy protocols have revealed that these activated cells are capable of mediating the regression of well established grossly visible tumor in visceral organs. Based upon these preclinical studies, a clinical trial is ongoing at the University of Michigan Medical Center in which these polyclonally activated T cells are used as therapy for patients with metastatic melanoma and renal cell carcinoma. Encouraging results in the ten patients treated for renal cell carcinoma, 5 responses (3 partial and 2 complete), have prompted us to initiate a new clinical trial to study the efficacy of these anti-CD3 mAB/IL-2 activated T cells in the treatment of advanced, unresectable squamous cell carcinomas of the head and neck. The basic design of this therapy will be first, vaccination of patients with autologous tumor cells in the presence of the potent immune adjuvant, BCG. Lymph node cells draining the vaccination site will be surgical retrieved and activated in vitro sequentially with OKT3 (anti-human CD3) and IL-2. These cells will by systemically infused into patients in conjunction with IL-2 treatment to promote anti-tumor cell survival and function. This new protocol for the treatment of squamous cell carcinoma has several aspects which make it unique and attractive for clinical investigation. While in vivo and in vitro studies have demonstrated that squamous cell carcinoma might represent an immunogenic tumor, clinical immunotherapeutic trials of this disease are lacking. Because of squamous cell carcinomas presumed immunogenicity, the potential advantage that might be derived from immunotherapy may be drastic. Additionally, unlike metastatic melanoma and renal cell carcinoma, squamous cell carcinoma of the head and neck tends to metastasize and recur regionally more readily facilitating tumor accession for vaccine development and clinical evaluation of observed treatment responses.